Drug abusers vary widely in their acute and chronic responses to drugs and in their compliance with and response to drug abuse treatment. A better understanding of the factors associated with individual differences in response should result in the development of more effective and efficient treatment interventions. This project assesses several biological and psychosocial characteristics of drug abusers and correlates them with abusers' response to their abused drug or to the abusers' treatment compliance and outcome. One component, in collaboration with Dr. Raymond Woosley, Department of Pharmacology, Georgetown University, measures activity of the plasma enzyme butyrylcholinesterase, the main cocaine-metabolizing enzyme in humans. Preliminary results indicate that cocaine addicts tend to have normal enzyme activity, which can vary four-fold between addicts. A second component assesses psychiatric co-morbidity, personality traits, mood, neuropsychological function, and social demographic characteristics in drug abusers using structured and semi-structured diagnostic interviews and computer-administered psychological tests. A third component, in collaboration with Dr. James Frost, Department of Radiology, Johns Hopkins University, uses positron emission tomography (PET) scanning to evaluate the effect of chronic cocaine abuse on mu- opiate receptor function in the brain, and the relationship between such receptor function and the severity and time course of cocaine withdrawal. Another component, in collaboration with the Molecular Neurobiology Laboratory, assesses various neurotransmitter-associated genotypes with the goal of identifying alleles significantly associated with particular substance use disorders.